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Patients with HD have motor, psychiatric and cognitive changes due to changes in a variety of neural circuits. Somatostatin-expressing interneurons (SST-INs) can regulate neural circuits largely by inhibiting their target cells. Behaviorally, brain-wide inhibition of SST-INs increased anxiety in mice. Silencing striatal SST-INs caused a decrease in movement in the open field. Mutant HTT (mHTT)-expressing mice exhibited abnormal motor, cognitive and psychiatric-like changes, as well as electrophysiological changes in a variety of neurons, including striatal SST-INs. However, it is unknown whether cell-autonomous expression of mHTT in SST-INs contributes to HD-associated behavioral phenotypes or causes abnormal electrophysiological changes in striatal SST-INs. To address these questions, we reduced mHTT expression in SST-INs throughout the brain of BACHD mice. Our findings show that brain-wide reduction of mHTT in SST-INs rescues anxiety-like behavior in male BACHD mice in the light\u2013dark box, without improving performance in the open field or on the rotarod. Additionally, expression of mHTT in striatal SST-INs cell autonomously drives their increased excitability.<\/jats:p>","DOI":"10.1242\/dmm.052513","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T11:17:41Z","timestamp":1770376661000},"source":"Crossref","is-referenced-by-count":0,"title":["Mutant huntingtin expression in somatostatin-positive interneurons contributes to neurophysiological and behavioral phenotypes in BACHD mice"],"prefix":"10.1242","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5708-6648","authenticated-orcid":false,"given":"Jahmel A.","family":"Fowler","sequence":"first","affiliation":[{"name":"Killion Center for Neurodegeneration and Experimental Therapeutics, The University of Alabama at Birmingham Heersink School of Medicine 1 Department of Neurology , , Birmingham, AL 35294 ,","place":["USA"]},{"name":"The University of Alabama at Birmingham Heersink School of Medicine 2 Graduate Biomedical Sciences, Biochemistry and Structural Biology Theme , , Birmingham, AL 35294 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6371-8568","authenticated-orcid":false,"given":"Mariangela","family":"Scarduzio","sequence":"additional","affiliation":[{"name":"Killion Center for Neurodegeneration and Experimental Therapeutics, The University of Alabama at Birmingham Heersink School of Medicine 1 Department of Neurology , , Birmingham, AL 35294 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cayla","family":"Pool","sequence":"additional","affiliation":[{"name":"College of Arts and Sciences, Xavier University of Louisiana 3 , New Orleans, LA 70125 ,","place":["USA"]},{"name":"Summer in Biomedical Sciences (SIBS) Undergraduate Research Program, The University of Alabama at Birmingham 4 , Birmingham, AL 35294 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Casey D.","family":"Mahan","sequence":"additional","affiliation":[{"name":"Killion Center for Neurodegeneration and Experimental Therapeutics, The University of Alabama at Birmingham Heersink School of Medicine 1 Department of Neurology , , Birmingham, AL 35294 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0808-108X","authenticated-orcid":false,"given":"Michelle","family":"Gray","sequence":"additional","affiliation":[{"name":"Killion Center for Neurodegeneration and Experimental Therapeutics, The University of Alabama at Birmingham Heersink School of Medicine 1 Department of Neurology , , Birmingham, AL 35294 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"2026032707145493500_DMM052513C2","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1016\/j.nicl.2018.03.027","article-title":"Reduced amygdala volumes are related to motor and cognitive signs in Huntington's disease: the IMAGE-HD study","volume":"18","author":"Ahveninen","year":"2018","journal-title":"Neuroimage Clin."},{"key":"2026032707145493500_DMM052513C3","doi-asserted-by":"publisher","first-page":"355","DOI":"10.3233\/JHD-180293","article-title":"Clinical management of neuropsychiatric symptoms of huntington disease: expert-based consensus guidelines on agitation, anxiety, apathy, psychosis and sleep disorders","volume":"7","author":"Anderson","year":"2018","journal-title":"J. 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